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81 Cards in this Set

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What is BK polyoma virus and polyomavirus nephropathy (PVN)
A non-enveloped DNA virus belonging to the Polyoma virus subfamily of Papovaviridae.

It causes polyomavirus nephropathy.
Describe the behavior of BK virus in the body.
It is a very common, asymptomatic infection (80-90% of the population is positive) - it persistently infects epithelial cells of the urinary tract.

Like herpes viruses, upon immunosuppression, BK virus reactivates and causes disease.
Describe polyomavirus nephropathy.
The BK virus causes an acute interstitial nephritis manifesting as renal dysfunction in 1-10% of renal transplant patients

Graft loss occurs in up to 90% of PVN cases
What virus may cause hemorrhagic cystitis in BMT recipients?
BK Polyoma virus
How is PVN treated?
Judicious reduction of immunosuppression regimen
What pathogen causes hemorrhagic adenovirus cystitis?
Adenovirus serotypes 11 and 21
Who gets hemorrhagic adenovirus cystitis? How is it different in transplant vs healthy patients?
Causes hemorrhagic adenovirus cystitis in renal transplant patients, pediatric BMT recipients, and healthy young boys.

In non-immunocompromised patients, cystitis is limited to a mild, self-limiting disease
What are some symptoms of hemorrhagic adenovirus cystitis?
Urgency
Frequency
Dysuria
May cause fever, hematuria, dyspareuria, abdominal cramps, and/or bladder pain and spasms
What drugs may be used to treat hemorrhagic adenovirus cystitis?
Vidarabine
Cidofovir
Ganciclovir
What is HIV-associated nephropathy?
Patients tend to present with a rapid decline in renal function, with a nephrotic syndrome consisting of proteinuria, azotemia, hypoalbuminemia, and hyperlipidemia.

*Not typically hypertensive*
What is the fourth leading cause of death in patients with HIV?
Kidney disease and renal failure
What are some problems that may look like HAN?
Medication toxicity
Volume depletion
Sepsis
Liver disease-induced causes of renal failure
Who is most susceptible to HAN?
Blacks with a polymorphism in the MYH9 gene (which encodes the non-muscle myosin heavy chain IIA protein) expressed in podocytes - plus HIV infection
What are the unifying pathological characteristics of HAN?
Hyperplastic injury within the glomerulus
Podocyte proliferation
Glomerular sclerosis
Tubular dilatation
Interstitial inflammation
How is HAN treated?
Aggressive treatment with HAART; steroids and angiotensin-converting enzyme inhibitors - mortality still reaches about 30%
How is glomerulonephritis induced by viral infection?
Cryoglobulinemia - immunoglobulins that precipitate in the cold but are soluble at body temperature. Some can form immune complex diseases.
What viruses are associated with glomerulonephritis from cryoglobulinemia?
Chronic viral infections like HIV, HBV, HCV
How does glomerulonephritis from cryoglobulinemia present?
Presents as renal disease and small vessel vasculitis, with palpable purpura, neuropathy, and lymphadenopathy

Associated with proteinuria, microscopic hematuria, impaired kidney function
What virus causes hemorrhagic fever with renal syndrome?
Hantaviruses - of family Bunyaviridae

Enveloped ssRNA viruses
What are some of the disease entities that cause hemorrhagic fever with renal syndrome?
Korean HF - Hantaan virus - in Europe and Asia
Seoul HF - Eastern Asia, Japan
Nephropathia endemica - Puumala virus - Scandinavia, NW Russia - more mild
What kind of renal damage is caused by hemorrhagic fever?
It causes an acute interstitial nephritis, with tubular necrosis

Pathology is due to damage to vascular endothelium.
Mechanism is unknown, but damage may be immune-complex mediated.
How is HFRS spread?
Spread by rodent contact only - aerosolization and inhalation of dried rodent urine or excreta
What are the symptoms of HFRS?
Illness may be moderate or severe, with fever, oliguria, proteinuria, abdominal pain, hemorrhaging.

Initial symptoms - fever, flushed face, periorbital edema, palatal and axillary petechiae, conjunctivitis, headache, eye pain, lumbar pain, TTP
How is HFRS treated?
Mortality rate from shock may be > 5%
Ribavirin has been used for KHF
Shock is managed with careful fluid replacement
A recombinant vaccine is available in Asia for KHF (Hantavax)
Give a few statistics about UTIs
20% of women have one before age 30
50% of women have a UTI at some point in their lives
40% of nosocomial infections are UTIs
25-50% of nursing home patients have bacteriuria at any time
What are the two categories for lower urinary tract infections?
Urethritis - of urethra
Cystitis - of bladder

Also considered superficial infections
What are the two categories for upper urinary tract infections?
Pyelonephritis - the kidney
Prostatitis - the prostate

Also considered invasive infections
What is the major defense mechanism against UTIs?
Flow of urine - cleanses, acidic
What is acute uncomplicated UTI?
Acute cystitis - common in healthy women
What is acute uncomplicated (non-obstructive) pyelonephritis?
Kidney infections - common in otherwise healthy women
What is a complicated UTI?
Bladder or kidney infections in individuals with underlying structural or functional abnormalities of the genitourinary tract (in men and women)
What is asymptomatic bacturia?
Bacteria in the urine without symptoms or signs attributable to UTI.
What is a renal abscess?
Uncommon - may occur with severe pyelonephritis or following bacteremia from other site of infection
Compare the susceptibilities of men and women to developing a UTI.
Females - higher susceptibility. Shorter urethra, proximity to source of infection, entry of bacteria is facilitated by sexual intercourse

Males - low susceptibility, longer urethra compared to women, antimicrobial substances in prostatic secretion, increased UTIs with prostate hypertrophy.
What are some factors that may increase the risk of developing a UTI?
Renal calculi
Ureteric reflex
Tumors in and adjacent to urinary tract
Pregnancy, Bladder Stones
Neurological problems
Incomplete bladder emptying large volume of residual urine
Loss of sphincter control
Prostatic hypertrophy
Short urethra in women
Catheterization
What are some bacterial factors that increase chance of a UTI?
Capsular antigens
Hemolysins
Urease
Adhesion to uroepithelium (P fimbrae in E. coli)
Introital colonization
What bacteria are most often responsible for uncomplicated UTIs?
Uncomplicated UTI

E. coli - 80-85% of cases
Staphylococcus saprophyticus - 5-15% of cases
Other Entereobacteriaceae - Proteus mirabilis, Klebsiella pneumoniae
What bacteria are most often responsible for complicated UTIs?
Complicated (or nosocomial) Infections

E. coli 20% of cases
The other 80% include...
Enterobacteriaceae - Proteus mirabilis, Klebsiella pneumoniae, Enterobacter, Serratia
Pseudomonas aeruginosa
Enterococcus species
Staphylococcus aureus
Describe the distribution of Enterobacteriaceae, and what kind of infections they cause.
Found worldwide, in soils and water
Normal intestinal flora

70% of UTIs
35% of Septicemias
Respiratory tract
CNS
GI tract
What are the microscopic and metabolic characteristics of Enterobacteriaceae?
Gram Negative Rods
Facultative anaerobes, no spores
Motile or Non-motile - may have flagella
Simple nutritional requirements, ferment glucose
Reduce nitrates to nitrites
Catalase Positive, Oxidase Negative

They have varying resistance to bile salts and fermentation abilities
What is the use of pili in Enterobacteriaceae?
Common fimbrae (pili) - adhesion to host cell
Sex pili - coded on conjugated plasmids, allows for genetic transfer between bacteria
What are some virulence factors of Enterobacteriaceae?
Exotoxins
Adhesion factors
Capsule
Antigenic phase variation
Type III secretion system
Antimicrobial resistance
What are the three components of Lipopolysaccharide?
1 - Outermost somatic O polysaccharide
2 - A core polysaccharide "Enterobacterial common antigen"
3 - Lipid A
How does LPS act as an endotoxin?
Lipid A is released as the cell lyses

It is a sign of systemic gram negative bacterial infections - complement is activated, cytokines released, leukocytosis, role in septic shock.
How are Enterobacteriaceae serotypes classified?
Based on 3 major groups of antigens
O - specific polysaccharides in outer membrane - always present
H - flagellar H proteins - motile cells only
K - capsular polysaccharide antigens, not always present
What are some characteristics of E. coli (microscopy, metabolic)?
Motile - peritrichous flagella
Ferments lactose
Urease negative
What are some common infections caused by E. coli?
UTI
Diarrheas/Dysentery
Neonatal meningitis
Septicemia
What are some of E. coli's virulence factors?
Adherence - P pilus (Pyelonephritis-associated pilus) binds digalactose receptor on uroepithelial cells
FimH - mannose sensitive pilus - binds mannosylated proteins that line the bladder mucosa
Motility
Hemolysin - pore forming cytotoxin
LPS
What are some characteristics of Proteus mirabilis?
Highly motile (peritrichous flagella)
Does not ferment lactose
Urease positive
What kinds of infections are caused by Proteus mirabilis?
Community and hospital-acquired UTIs
Pneumonia
Septicemia
Wound infections
What are some virulence factors of Proteus mirabilis?
Adhesins
Motility - swarming
Endotoxin - inflammatory response
Urease production - increases urine pH, which is toxic to renal cells and potentiates the formation of calculi.
What are some characteristics of Klebsiella pneumoniae?
Non-motile
Ferments lactose
Urease negative
What are some infections caused by Klebsiella pneumoniae?
UTIs - community, nosocomial
LRTI - lobar pneumonia in infants, elderly, alcoholics, chronic lung disease

Often transmitted via catheters
What are some virulence factors of Klebsiella pneumoniae?
Pili - adherence to urinary epithelium
Polysaccharide capsule - interferes with complement activation, antiphagocytosis
Endotoxin - causes fever, inflammation
What are some characteristics of Enterobacter sp.?
Motile - peritrichous flagella
Ferment lactose
Urease negative

Cause nosocomial infections
What are some virulence factors of Enterobacter?
Adhesins
Capsule * Major virulence factor *
Endotoxin
Where are Serratia sp. found?
Habitat is the gut of humans and animals, environment as well
What is the name of the only pathogenic species of Serratia?
Serratia marescens
What are some characteristics of Serratia?
Slow lactose fermenter
Produce a red pigment, distinctive brick-red colonies
Cause nosocomial infections
What are some virulence factors of Serratia?
Adhesins
Capsule
Endotoxin
How is Enterobacteriaceae identified?
Urine culture
Plate on MAC agar,
What are the various Lactose fermenting abilities of E. coli, K. pneumoniae, Enterobacter, Serratia, and P. mirabilis?
Lactose Fermenters - E. coli, K. pneumoniae, Enterobacter
Slow Lactose Fermenter - Serratia
Does not ferment lactose - P. mirabilis
What are two additional tests, besides lactose, that are used to identify P. mirabilis?
Swarming motility test (positive)
Urease test (positive)
What are some characteristics of Pseudomonas aeruginosa?
Aerobic Gram Negative Rod
Motile
Oxidase positive
No Fermentation
Adapt to low nutrients

Cause a variety of opportunistic infections
What are the virulence factors of Pseudomonas aeruginosa?
Adhesins - adhere to epithelial cells
Polysaccharide capsule - protect from phagocytosis/opsonization
Endotoxin - inflammation
Extracellular enzymes and toxins - Exotoxin A - tissue damage
How is Pseudomonas aeruginosa diagnosed?
Microscopy - gram negative rods

Culture - blue-green colonies with procyanin/pyoverdin, fluorescein, grows at 42 degrees, fruity aroma, mucoid, fluoresces
What are some characteristics of Staphylococcus aureus?
Gram positive cocci
Irregular clusters - grapelike
Catalase positive
Coagulase negative

Facultative anaerobe
Phosphatase negative
Urease and lipase positive

S. saprophyticus causes 10-20% of UTIs in sexually active young women
What are some virulence factors of S. saprophyticus?
Transmission - endogenous spread
Adhesin
Elicits an inflammatory response
How is S. saprophyticus diagnosed?
Urine culture - growth on blood agar, gamma hemolysis, novobiocin resistant

Gram positive cocci in irregular clusters

Coagulase negative
What are some characteristics of Enterococcus faecalis/faecium?
Gram positive diplococci or short chains
Catalase positive
Lancefield's group D antigen
Facultative anaerobes

Most infections from endogenous flora
What kinds of infections are caused by Enterococcus faecalis/faecium?
UTI
Endocarditis
Wound infections
Bacteremia
What are some virulence factors of Enterococci?
Adhesins
Toxins and enzymes, tissue damage - cytolysin, gelatinase, serine protease

All strains carry some drug resistance
How is Enterococci diagnosed?
Urine culture - gamma or alpha hemolytic on blood agar

Resistant to 40% bile salts, 6.5% NaCl, Bacitracin, Optochin

Microscopy - Gram positive cocci, short chains

PYR (L-pyrrolidonyl-B-naphthylamide) test - to detect presence of pyrrolidonyl peptidase
Describe the clinical presentation of Cystitis.
Generally NO invasion of mucosa, it is superficial irritation

Dysuria
Urgency
Frequency
Urine cloudy
Gross hematuria in 50% of cases
No fever or systemic manifestation of illness
Describe the clinical presentation of Pyelonephritis.
Invasive disease - may be preceded or accompanied by manifestations of Cystitis

Flank pain, tenderness
Systemic manifestations: Fever, chills, more severely ill patients have vomiting, diarrhea, tachycardia
What is the clinical presentation of Prostatitis?
Pelvic and low back pain
Acute infection with high fever, dysuria, frequency
Inflammatory swelling - obstruction of urethra and urine retention

Chronic prostatitis - low-grade pain and dysuria when symptoms are present, cause recurrent bacteremia in men
How are urine samples obtained?
Clean-void technique - clean area, catch midstream

Catheterization

Suprapubic aspiration
What lab results are necessary for a positive UTI diagnosis?
Colony count must be > 10^5 CFU/mL of urine
That is considered infection or "significant bacteriuria"
30-50% of women with acute cystitis have lower counts
What microscopy results would indicate UTI?
90% of patients with acute symptoms of UTI have pyuria
Gram stain
What dipstick results indicate possible UTI?
Positive leukocyte esterase test - tests for the presence of leukocytes in the urine
How are UTIs treated?
Antibiotics

Acute uncomplicated cystitis - 3 days TMP-SMZ

Acute uncomplicated pyelonephritis, complicated UTI, resistant organisms - Fluoroquinolone 10-14 days, check cultures later

Pregnant women - Cephalosporin

Complicated UTI - hold off on therapy until cultures come back

Increase fluid intake